Twin Research and Human Genetics

Background: Maternal obesity is associated with lower breastfeeding initiation, shorter breastfeeding duration and lower rates of exclusive breastfeeding. Although breastfeeding intention predicts initiation, little is known about how first-time mothers living with obesity experience the transition from antenatal intention to postpartum reality. Aim: This qualitative study explored breastfeeding expectations, intentions, attitudes and early breastfeeding challenges among first-time mothers living with obesity in Switzerland. Methods: Seven semi-structured interviews were conducted with first-time mothers living with obesity in German-speaking Switzerland. Interviews were audio-recorded, transcribed verbatim and analysed using reflexive thematic analysis according to Braun and Clarke. Results: All participants intended to breastfeed and described breastfeeding as part of motherhood. However, most experienced a postpartum reality that differed from their expectations. Three themes were developed: antenatal engagement with and expectations of breastfeeding, postpartum breastfeeding reality, and everyday breastfeeding life. Women received little antenatal breastfeeding counselling and faced challenges related to medicalised birth, delayed lactogenesis II, breast anatomy, pain, insufficient milk supply, pumping and inconsistent professional support. Several women described feelings of failure when breastfeeding did not work as hoped. Conclusion: First-time mothers living with obesity may have strong breastfeeding intentions but still experience major challenges after birth. Breastfeeding support should start during pregnancy and be realistic, respectful and weight-inclusive.

Background: Poor prenatal sleep health is associated with greater gestational weight gain, but the contributions to longer-term maternal weight retention remain unclear. Purpose: To examine associations between prenatal sleep health across multiple domains and maternal weight retention 2 to 7 years after a first birth. Methods: Participants were from the nuMoM2b-Heart Health Study. Self-reported sleep was assessed during early (6 to 13 6/7 weeks) and mid-pregnancy (22 to 28 6/7 weeks) across six domains: regularity, quality, sleepiness, timing, efficiency, and duration. A multidimensional sleep health (MSH) score reflected the number of domains meeting healthy thresholds. Outcomes included maternal weight retention, total and substantial (>11 lbs.), from pre-pregnancy to 2 to 7 years after a first birth. Associations were estimated using adjusted linear regression for total weight retention and Poisson regression with robust variance for substantial weight retention. Results: The sample included 3,661 individuals with data in early (n = 2,962) and mid-pregnancy (n = 3,210). In early pregnancy, healthy sleep duration was associated with lower total weight retention, whereas healthy sleep regularity was unexpectedly associated with greater retention. In contrast, during mid-pregnancy, a higher MSH score was associated with a lower risk of substantial weight retention (RR = 0.96, 95% CI: 0.93 to 0.99). Healthy sleep duration and quality were the two individual domains associated with lower weight retention (2 to 3 lbs.). Conclusions: In a prospective cohort of pregnant nulliparous individuals, healthy prenatal sleep, particularly during mid-pregnancy, was associated with less maternal weight retention 2 to 7 years after delivery. Future studies should estimate the causal effects of sleep health on long-term maternal weight retention.

Background: Stress research in nursing education has largely focused on distress, stressors, and negative outcomes, although challenging experiences may also support motivation, confidence, learning, and growth when appraised positively. Objective: To develop and evaluate the psychometric properties of the Nursing Student Positive Stress Scale (NSPSS). Design: A methodological instrument development and psychometric evaluation study. Methods: The NSPSS was developed using a deductive, theory-driven approach informed by the transactional theory of stress and coping and positive psychology perspectives. Content validity was assessed by an international nursing expert panel. Psychometric evaluation used national survey data from nursing students in New Zealand. Of 539 responses, 507 were analysed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted using separate subsamples. Internal consistency was assessed using Cronbach's alpha and McDonald's omega, and convergent validity through correlation with Perceived Stress Scale-10 scores. Results: Content validity was strong (I-CVI = .88-1.00; S-CVI/Ave = .975; S-CVI/UA = .800). EFA identified a dominant factor explaining 41.38% of variance (loadings = .528-.735). CFA supported a two-context Academic and Clinical Positive Stress model with correlated residuals between five parallel item pairs, chi-square(29) = 60.49, CFI = .970, TLI = .954, RMSEA = .063, SRMR = .065. Internal consistency was good (alpha = .839; omega = .843). NSPSS scores correlated negatively with PSS-10 scores (r = -.298, p < .001). Conclusion: The NSPSS demonstrated strong content validity, preliminary evidence of structural and convergent validity, and good internal consistency reliability for assessing positive stress appraisal among nursing students. Further validation in independent samples is warranted.

Background: Cardiometabolic health typically declines with age and is worse among individuals living with obesity. Weight loss medications have modified the potential for weight loss across the life course, but it remains unclear whether weight reduction in later midlife contributes to improved cardiometabolic health, or if continuing to gain weight may continue to worsen cardiometabolic health. Methods: Using the nationally representative 1958 National Child Development Study (NCDS), a British birth cohort, associations were examined using lagged linear regression between weight change between ages 50-55 and health outcomes at age 62 (n=6,309 high-density lipoprotein (HDLc) and low-density lipoprotein (LDLc) cholesterol, systolic and diastolic blood pressure (SBP and DBP), heart rate, triglycerides, C-reactive protein (CRP), and glycated haemoglobin (HbA1c). Models accounted for prior biomarker levels at age 44. We also explored impacts of weight change on subsequent body composition. Results: Those who gained weight into or within obesity had less favourable cardiometabolic profiles and experienced faster deterioration of cardiometabolic markers between the ages of 44 and 62 than those remaining in healthy weight (e.g. SBP: 5.726, 95% CI: 2.660 to 8.793, p < 0.001; CRP: 0.802, 95% CI: 0.409 to 1.196, p < 0.001). Those who lost weight from obesity had similar rates of cardiometabolic biomarker deterioration to the healthy weight group (SBP: 0.947, 95%CI: -6.605 to 8.499, p=0.806; CRP: 0.140, 95% CI: -0.774 to 1.055, p= 0.764). Conclusion: Weight change in midlife tends towards increasing obesity and associated adverse cardiometabolic risk. Those who lose weight experienced improved cardiometabolic profiles. By viewing midlife as a modifiable stage of the life course, this study highlights opportunities to promote cardiometabolic health, and limit the speed of health decline.

Background. DNA methylation patterns in cord blood are robustly associated with birthweight in the general population. However, it remains unknown whether these associations extend to clinically relevant populations, such as preterm neonates or those born small for gestational age, and whether they directly reflect birthweight or are driven indirectly by genetic, familial, maternal, and obstetric factors. Methods. We calculated a birthweight methylation profile score (MPSBW) using weights of 835 CpGs previously associated with birthweight in the general population and evaluated its association with birthweight in 67 monochorionic (MC) twin pairs including 134 neonates (97% born preterm) from the Twinlife study. MC twin pairs are identical twins sharing a single placenta, often unequally, which can result in unequal resource distribution and differential fetal growth. Results. We examined the association between within-pair differences in birthweight and MPSBW, thereby estimating the association independent of factors shared equally by co-twins. A 500-gram increase in birthweight was associated with a 0.256 SD increase in MPSBW (p<0.005) in this population of preterm neonates. Adjustment for polygenic score for birthweight (PGSBW) confirmed that the observed epigenetic associations were not driven by common genetic variation underlying birthweight. Interestingly, a similar effect size (0.226 SD per 500 g birthweight increase; p<0.05) was observed in the within-pair analysis, which controls for all shared influences within a twin pair. Conclusion DNA methylation is associated with individual differences in birthweight in a high-risk clinical population of MC twins, independent of shared genetic, familial or maternal influences.

Abstract Aim: Examine cross-sectional associations between mid-pregnancy food intake indicators and prenatal depressive symptomatology. Methods: This secondary analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial (N = 718) examined domains of mid-pregnancy food intake (direct timing, energy timing, meal/snack structure, meal energy distribution, diet quality) derived from 24-hour dietary recalls. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Generalized linear models examined associations between food intake indicators, total, and high (EPDS [&ge;]13) depressive symptoms. Results: Mean (SD) EPDS score was [6.3 (4.9)]; 12.4% (n = 89) had high depressive symptoms. Eating frequency (B = 0.08 [0.02, 0.14], p = 0.009), snack frequency (B = 0.06 [0.00, 0.12], p = 0.040), nighttime snacking frequency (B = 0.06 [0.00, 0.11], p = 0.041), and total daily energy intake (B = 0.06 [0.01, 0.12], p = 0.031) were positively associated with total depressive symptoms. Energy intake from breakfast (PR = 1.2 [1.0, 1.3], p = 0.017) was associated with a higher prevalence of high depressive symptoms. Energy intake from dinner (PR = 0.81 [0.69, 0.94], p = 0.007), later timing of the first eating episode (PR = 0.83 [0.70, 0.99], p = 0.034) and first energy quartile (PR = 0.84 [0.70, 1.0], p = 0.048), were associated with a lower prevalence of high depressive symptoms. Conclusion: These findings extend prior chrononutrition-depression literature to the prenatal period, implicating eating frequency, energy intake, and meal energy timing and distribution in depressive symptomatology during pregnancy, warranting further longitudinal investigation.

Background: Inequalities exist for many health outcomes, but there is limited evidence regarding menstrual symptoms despite their importance for health and wellbeing. We aimed to investigate inequalities in menstrual symptoms according to socioeconomic position and childhood adversity. Methods: In two generations (G0 mothers and G1 offspring) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK prospective cohort study, we examined associations of multiple indicators of socioeconomic position (SEP) and adverse childhood experiences (ACEs) with menstrual symptoms (pain, abnormal uterine bleeding, and premenstrual syndrome (PMS) measured 3-8-years post-birth in G0 and 17-21-years-old in G1), using multivariable logistic regression. Samples ranged from 4,828 to 9,335 G0 participants and 1,288 to 2,757 G1 participants depending on the exposure-outcome association. Missing data were addressed using multiple imputation and inverse probability weighting. Results: Financial difficulties were associated with greater odds of menstrual pain (G1 OR 1.41; 95% CI 1.07, 1.86: G0 OR 1.55; 95% CI 1.36, 1.76) and irregular cycles (G1 OR 1.60; 95% CI 1.12, 2.29: G0 OR 1.48; 95% CI 1.27, 1.72) in both generations, as well as with short/long cycle lengths in G0 only. Lower education and manual social class were also associated with these three menstrual symptoms in at least one generation. Conversely, higher SEP was associated with PMS in both generations. Higher cumulative ACEs were consistently associated with menstrual pain (4+ compared to none: G1 OR 2.15; 95% CI 1.48, 3.11: G0 OR 1.52; 95% CI 1.29, 1.80) and irregular cycles (G1 OR 1.92; 95% CI 1.20, 3.09: G0 OR 1.54; 95% CI 1.26, 1.87) but not cycle length. Lower parental education, financial difficulties, and cumulative ACEs were associated with heavy bleeding in G1 offspring only, whereas financial difficulties, own manual social class, and cumulative ACEs were associated with prolonged bleeding in G0 mothers only. Higher cumulative ACEs were also associated with PMS in G1 offspring only. Conclusions: We found evidence of inequalities according to socioeconomic disadvantage and childhood adversity for multiple menstrual symptoms, although some associations were only observed in one generation. Findings suggest that menstrual symptoms are disproportionately experienced by socially and socioeconomically disadvantaged women.

Abstract Importance: Socially vulnerable patients have a high burden of obstructive sleep apnea, but the stage of the referral pathway at which access barriers arise is uncertain. Objective: To determine whether area-level social deprivation was associated with appointment scheduling, wait time, cancellations, or no-shows among adults referred for specialist obstructive sleep apnea care. Design: This was a cross-sectional study evaluating patients referred from December 1, 2016 through November 30, 2019. Data were analyzed from January 30, 2026 to May 16, 2026. Setting: Foothills Medical Centre Sleep Centre in Calgary, Canada. Participants: Adults referred to a tertiary academic sleep centre in Calgary, Alberta, Canada. Eligible patients had valid provincial health insurance and either a scheduled clinic appointment or home sleep apnea test data available. Exposures: Quintiles of the four Canadian Index of Multiple Deprivation domains: residential instability, economic dependency, ethnocultural composition, and situational vulnerability. Main Outcomes and Measures: The primary outcome was receipt of a scheduled specialist appointment. Secondary outcomes were time from referral to the first attended appointment and number of appointment cancellations or no-shows. Results: Among 3111 patients (mean [SD] age, 53.7 [14.3] years; 40.7% female), 1766 (56.7%) were scheduled and 1647 (52.9%) attended an appointment. Each quintile increase in situational vulnerability was associated with lower odds of scheduling (adjusted odds ratio [95% confidence interval] 0.86 [0.81-0.92]), whereas each quintile increase in ethnocultural composition was associated with higher odds (adjusted odds ratio [95% confidence interval] 1.32 [1.22-1.43]). Residential instability and economic dependency were not associated with scheduling. No deprivation domain was associated with time to the first attended appointment, cancellations, or no-shows. Conclusions and Relevance: In this cohort, area-level deprivation was associated with whether patients were scheduled for an appointment but not with wait time or missed visits after scheduling. These findings suggest that equity interventions should focus on completion of referral and scheduling processes.

A body of research suggests that autistic individuals are less likely to drink alcohol than neurotypicals. However, emerging studies support a link between autism and alcohol use. This complex relationship is also reflected in studies that have examined the genetic overlap between the two traits. However, it is unclear whether there is a direct causal relationship between them. To explore this, we applied a combination of polygenic score and Mendelian randomisation analyses using publicly available genome-wide summary statistics and phenotypic measures of autism and alcohol consumption from UK Biobank. LD score regression analyses did not provide evidence of a genetic correlation between genetic liability for autism and drinks consumed per week (rg=-0.08; CI95%=-0.19, 0.03). Further, findings from polygenic score analyses did not support an association between genetic liability for autism and overall monthly alcohol intake. Univariable Mendelian randomisation analyses showed little evidence for a total effect of autism, attention deficit hyperactivity disorder (ADHD) or depression on overall monthly alcohol consumption. Multivariable Mendelian randomisation analyses also showed little evidence of a direct effect of autism on drinks per week when controlling for ADHD and depression. It is plausible that genetic liability for autism does not directly increase the amount of alcohol consumed but instead operates via commonly co-occurring difficulties in the autistic community. However, our findings may be due to methodological shortcomings, including weak instruments biasing effects towards to the null. Consequently, results should be interpreted with caution and further research conducted to address these issues.

Obesity is a growing public health challenge, with body mass index (BMI) influenced by both genetic and environmental factors. While the role of direct genetic transmission is well established, evidence for genetic nurture effects, in which parental genotypes impact offspring through the environment, has remained mixed. This study investigates direct genetic transmission and genetic nurture effects on BMI across ages, using parent-offspring trios and pairs from the Dutch Lifelines cohort study (N = 18,897 offspring, aged 8 to 67 years). We leveraged the latest multi-ancestry BMI polygenic score (PGS) to construct transmitted (PGS-T) and non-transmitted (PGS-NT) polygenic scores, where PGS-NT consists of parental alleles not passed on to offspring and serves as a proxy for genetic nurture. Linear mixed models showed a large effect of PGS-T on offspring BMI (Beta = 0.416, p < 0.001), corresponding to a 1.85 kg/m2 increase per SD increase in PGS-T. PGS-NT had a small but significant effect (Beta = 0.026, p = 0.013), consistent with a genetic nurture effect accounting for approximately 6.6% of the effect of direct transmission. Parent-of-origin analyses showed that maternal PGS-NT effects were larger than paternal effects. PGS-T interactions with age indicated that direct transmission effects increased in childhood and stabilized in adulthood, while PGS-NT effects remained stable across age. Our findings suggest that direct genetic transmission is the dominant influence on BMI, while results are consistent with small genetic nurture effects that are driven by the maternal side.

Adverse experiences in childhood (AEs) typically refer to undesirable events, including child maltreatment and household challenges. Various survey measures and linked routine data in the Born in Bradford Birth Cohort (BiB) datasets can provide a contemporary understanding of the distribution of AEs in the population and the factors related to their occurrence. This study aimed to identify relevant survey data on AEs collected from BiB families and to summarise the prevalence of AEs from birth to early adolescence (ages 12-15) among BiB children. We included BiB children who participated in the follow-ups - Growing Up (GUp, n=5253) and Age of Wonder (AoW, n=2662). Four AEs were identified - parental mental illness, parental substance use, children not living with both parents in the same home, and being bullied by peers. The survey data included 1) health, substance use, living arrangements, and children's bullying experience reported by parent(s) at baseline (2007-2011, around birth) and/or GUp (2017-2022, during mid-childhood), and 2) bullying experience and living arrangements self-reported by children at AoW (2022-2024, during early adolescence). Additionally, we included parents' primary care records regarding any mental illness or substance use. Overall, 3371 (64.2%) children experienced at least one of the four AEs between birth and early adolescence. The most common AE was parental mental illness, whereas parental substance use was the least common. Children across all sociodemographic groups experienced AEs. Asian children, or those whose mothers were not materially deprived, appeared less likely to experience AEs. Conversely, children of White or Mixed ethnicities, or whose mothers were materially deprived, were more likely to experience AEs. Consistent with similar studies, our findings show that AEs are widespread but disproportionately affect certain sociodemographic subgroups among BiB children. These disparities can be reduced by early-years policies that provide practical family support, guided by continuously collected AE data.

Chronotype is a complex trait reflecting individual differences in the temporal organization of rest and activity, with important health implications. The Uruguayan population, characterized by a tri-hybrid origin (African, European, and Indigenous), exhibits a bias toward eveningness. The genetic variation in clock genes underlying chronotype in this population remains unexplored. To address this gap, we analyze healthy young adults from the extremes of the chronotype distribution (early, n = 37; late, n = 38; 63% female; 23.1 {+/-} 3.4 years), integrating self-reported measures, actigraphy, and low-pass whole-genome sequencing. Global ancestry is predominantly European, with Indigenous and African components, and does not differ between chronotypes. Variant density is highest in PER2. T-allele carriers of a PER2 variant previously associated with late chronotypes (rs35333999) differ from non-carriers in activity acrophase. Multidimensional scaling of variants across 19 canonical clock genes reveal differential representation of early and late chronotypes across genetic clusters. When examined by functional groups, the signal is restricted to genes involved in degradation of the circadian clock's repressor arm, with BTRC, a mediator of PER2 degradation, showing the same pattern when assessed individually. We derive a joint behavioral component capturing the variation in food intake, moderate-to-vigorous physical activity, light exposure, and sleep timing, which correlates with dim-light melatonin onset (DLMO), the gold-standard marker of circadian phase, and show differences among genetic clusters. Our integrative multilevel approach suggests a complex interplay between behavioral and genetic factors shaping chronotype in this cohort, highlighting the PER2BTRC axis as a candidate mechanism for future investigations.

Childhood peer victimization is increasingly recognized as an adverse childhood experience (ACE) with long-term consequences for population health. Most existing research treats bullying as a binary exposure, obscuring the dose-response mechanisms through which cumulative victimization generates escalating health risks. This methodological gap is particularly consequential for prevention, and evidence from the Gulf Cooperation Council (GCC) region remains systematically sparse. This study conducts a national dose-response analysis of childhood bullying and adult health outcomes in Saudi Arabia using the WHO Adverse Childhood Experiences International Questionnaire (ACE-IQ), administered to a nationally representative sample of 10,156 adults by the King Abdullah International Medical Research Center (KAIMRC) and the National Family Safety Program (NFSP), Ministry of National Guard Health Affairs (2013). We conducted a cross-sectional secondary analysis examining associations between bullying frequency and five adult health outcomes: physician-diagnosed anxiety disorder, suicidal ideation, sleep disturbance, tobacco smoking, and substance use. The analytical sample comprised 4,632 adults reporting any childhood peer victimization. Binary logistic regression models adjusted for socioeconomic status, gender, age cohort, parental supervision, and family structure were estimated separately for each outcome. Three pre-specified hypotheses were tested: (H1) any bullying exposure is associated with higher odds of adverse adult health outcomes; (H2) increasing frequency follows a dose-response gradient; and (H3) associations are amplified among socioeconomically disadvantaged respondents and attenuated among those reporting higher parental attention. A consistent dose-response gradient was observed. Frequent victims showed substantially higher adjusted odds of tobacco smoking (OR = 6.55, 95% CI 5.81-7.32) and substance use (OR = 2.71, 95% CI 2.26-3.31) compared to those never bullied. Internalizing outcomes showed significant gradients for anxiety disorder (OR = 0.37, 95% CI 0.16-0.86) and sleep disturbance (OR = 0.39, 95% CI 0.20-0.76). Religion-targeted verbal victimization was the strongest independent predictor of suicidal ideation (OR = 3.01, 95% CI 1.83-4.97) and substance use (OR = 3.24, 95% CI 1.92-5.46), independent of bullying frequency. Bullying-health associations were significantly amplified among socioeconomically disadvantaged respondents, consistent with fundamental cause theory. Parental supervision was protective against substance use (OR = 0.45, 95% CI 0.30-0.67) but showed a paradoxical positive association with suicidal ideation, interpreted as a reactive parenting effect in the cross-sectional design. These findings establish childhood bullying as a cumulative, graded public health risk whose consequences are amplified by structural disadvantage. Prevention strategies must extend beyond school-level programs to address structural inequalities and integrate family-based and community-level protective factors. This study contributes population-level ACE evidence from the underrepresented GCC region and provides a foundation for integrating bullying prevention into Saudi Arabia's Vision 2030 national health agenda.

Background & aims: The human gut microbiota plays a key role in health. Factors shaping its composition and diversity have been widely studied during infancy and adulthood, but far less in adolescence, despite this being a key developmental stage. We examined the potential associations between the gut microbiota of adolescents and 82 variables measured from pregnancy to adolescence. Methods: Stool samples were collected from 366 adolescents (age range: 13-16 years) from two INMA cohorts (Spain), while a range of variables, including diet, lifestyle, sociodemographic factors, health status, antibiotic use, vaccination, COVID-19, anthropometrics, and pubertal development, were collected from pregnancy to adolescence. The gut microbiota was characterized using 16S rRNA gene sequencing and assessed using - and {beta}-diversity indices and individual taxa. Associations with the study variables were evaluated using linear models, permutational multivariate analysis of variance (PERMANOVA), and Microbiome Multivariable Association with Linear Models (MaAsLin2). Results: During pregnancy, vegetable intake was positively associated with -diversity and with both {beta}-diversity and the abundance of four genera (three inverse associations and one positive association). Legume intake was also inversely associated with two genera. During adolescence, cereal and pasta intake was positively associated with -diversity and {beta}-diversity, and was inversely associated with Bacteroides, whereas fish and seafood intake was inversely associated with -diversity. Other relevant variables measured during pregnancy and at birth, such as biological sex, parental social class, and maternal education, and during adolescence, such as antibiotic use, body mass index, and pubertal status, were also associated with {beta}-diversity indices and different taxa in both directions. Conclusions: Diet during pregnancy and adolescence, together with some anthropometric, clinical, and biological factors, appeared to play an important role in shaping the composition and diversity of the gut microbiota in this population of adolescents.

In characterizing sleep and circadian health, the day-to-day regularity of sleep-wake timing strongly predicts health outcomes, outperforming short sleep duration in prospective associations with mortality and new-onset disease. It is unknown whether biological (e.g., sleep and circadian physiology) and sociocultural (e.g., exposures that affect sleep-wake timing) sex differences lead to differences in day-to-day sleep-wake regularity or modify its prospective associations with health outcomes. Here, we present findings from a UK Biobank study of 506,582 person-days of accelerometer recordings across 73,647 middle-aged adults preceding 549,009 person-years of follow-up. We compared SRI scores between males and females and evaluated whether all-cause, cardiovascular, and cancer mortality differed across SRI groups by sex. Custom contrasts were used to compare estimated marginal means across specific SRI-sex combinations. Females were overrepresented among very high (SRI [&ge;]90) and underrepresented among very low (SRI <60) groups. After adjustment for demographic, health, and behavioral covariates, males still had higher odds than females of exhibiting SRI <60. Low SRI and male sex were synergistically associated with higher mortality rate. Demographic, health, and behavioral covariate-adjusted models showed stronger and more dose-dependent associations between low SRI and mortality among males than females. Although the omnibus SRI x sex interaction terms were not statistically significant, the interaction contrast for SRI <60 versus [&ge;]90 differed by sex, suggesting a possible sex difference in mortality rates at very low SRI. Together, our findings suggest that males may be more vulnerable than females to the mortality risk associated with highly irregular sleep-wake schedules.

Resolving the inner conflict between improving eating habits (change talk) and sticking to unhealthy ones (sustain talk) is a key target in communication-based behavioral change interventions such as motivational interviewing (MI). Recent work has shown that this inner conflict affects how tastiness and healthiness are traded off in dietary decision-making. The effect varied with body mass index (BMI). Here we aimed to identify why participants with higher BMI shifted toward healthier food choices after listening to change talk. An evidence accumulation model found that BMI affected health evidence sampling when listening to change talk, and taste evidence sampling when listening to sustain talk. A serial mediation analysis showed that the effect of BMI on change-talk-induced health evidence sampling was explained by stronger resting-state connectivity in the ventromedial prefrontal cortex within the default mode network (DMN), which in turn predicted greater motivation to change eating habits. These cross-sectional findings indicate that the intrinsic functional organization of valuation-related regions within the DMN is associated with motivation to change. They provide evidence that these neural and behavioral factors need to align with contextual cues, such as weight status (as reflected by BMI), and with reasons for behavioral change to promote healthier decision-making.

Objective: To examine changes in the neural valuation of high- versus low-calorie stimuli following bariatric surgery and determine whether these changes relate to weight loss at 24 months. Methods: Adults undergoing bariatric surgery completed fMRI scans before surgery and at 4, 12 and 24 months post-surgery while performing the Becker-DeGroot-Marschak auction task to assess willingness-to-pay (WTP) for food stimuli. Linear mixed-effect models tested longitudinal changes in WTP-related blood oxygen level-dependent (BOLD) associations and their interactions with total weight loss at 24 months. Results: WTP for high-calorie foods decreased significantly after surgery, whereas valuation of low-calorie foods remained stable. At 4 months, WTP-BOLD associations for high- versus low-calorie stimuli were enhanced within the frontoparietal control network and right lateral orbitofrontal cortex relative to pre-surgery. These early postoperative changes did not correlate with 24-month weight loss. Instead, greater 24-month weight loss correlated with both pre-surgical and long-term changes (24 months versus pre-surgery) in WTP-BOLD associations within the precuneus, inferior parietal cortex and visual cortex. Conclusion: Bariatric surgery induces early reductions in the valuation of high-calorie foods, potentially through enhanced cognitive control and aversive processing. However, long-term weight-loss success appears more strongly related to trait-like neural differences in self-referential and attentional processing.

Body mass index (BMI), visual function and resting heart rate (RHR) are standard measurements in adolescent physical examinations, yet their interconnections and age- and gender-specific differences are not fully clarified. This multicentre retrospective cohort study analyzed 130,832 screening records of 8-17-year-old adolescents from 2022 to 2024, using mixed-effects models and stratified analyses to examine BMIs independent correlations with UCVA (UCVA) and RHR, alongside the moderating effects of age and sex. Boys presented higher BMI values and greater overweight/obesity prevalence, whereas girls had poorer UCVA. After adjusting for confounders, every 1 kg/m{superscript 2} increment in BMI correlated with a -0.008 log MAR change (a stronger effect in girls) and a 0.26 beat-per-minute rise in RHR. The inverse BMI-UCVA correlation peaked at ages 8-11, weakened among 12-16-year-olds, and reversed at age 17. RHR decreased steadily with age, being marginally lower in boys, with a notable age-sex interaction. Age and sex jointly shaped the correlations among the three indicators, whose statistically significant links varied across developmental periods. Therefore, integrated screening should assess all indicators comprehensively while accounting for age and gender disparities. We propose unified, sex and age-stratified adolescent screening and intervention strategies to simultaneously mitigate obesity, myopia and cardiovascular risks, rather than isolated single-disease prevention.

Importance The menopausal transition has been associated with an increased risk of depression, although findings are inconsistent. While most research has focused on menopausal stage, some studies suggest that later age at menopause may be associated with lower depression risk. Objective To examine the association between age at menopause and depression risk during perimenopause and early postmenopause using multivariable regression and genetic approaches. Design Prospective cohort study using data from the mothers of the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort that recruited pregnant women in 1991-1992. Setting UK community-based cohort study. Participants Up to 3,307 women with repeated measures of depressive symptoms across the perimenopausal and postmenopausal periods and data on observed or genetically predicted age at menopause. Exposure Observed age at menopause, a polygenic risk score (PRS) for age at menopause, and genetically predicted age at menopause. Main Outcome(s) and Measure(s) Depressive symptoms during the perimenopausal and early postmenopausal periods were assessed using the Edinburgh Postnatal Depression Scale (EPDS), with depression defined as a score >= 13. Results Effect estimates across multivariable regression and genetic analyses were small and directionally consistent with lower odds of depression with older age at menopause, although most confidence intervals included the null. In analyses using observed age at menopause, there was little evidence of an association with depression during perimenopause (Odds ratio (OR) per year increase in age at menopause 0.98, 95%CI 0.89-1.08) or postmenopause (OR 1.00, 95%CI 0.89-1.13). Results were similar when using a PRS as a genetic proxy for age at menopause during perimenopause (OR per standard deviation (SD) increase in PRS 0.98, 95%CI 0.89-1.09) but suggested lower odds of depression during postmenopause (OR 0.92, 95%CI 0.86-0.99). Mendelian randomization analyses did not support a causal effect (OR per year increase 1.00, 95%CI 0.89-1.13 for perimenopause, and OR 0.97, 95%CI 0.86-1.09 for postmenopause). Conclusions and Relevance Age at menopause is unlikely to be a major driver of midlife depression risk. However, consistent effect directions across approaches suggest a small association may exist, but further research in larger samples is needed to confirm this.

Abstract Purpose: Haemochromatosis due to HFE-C282Y homozygosity can lead to excess iron absorption and is typically associated with liver malignancy, plus widespread arthritis. Recent evidence suggests that limb fractures are more common, but little is known about vertebral effects. This study investigated the association of vertebral compression fractures, assessed with intelligent dual-energy X-ray absorptiometry (iDXA), and HFE genotype in a large community cohort. Methods: UK Biobank data from 227 European genetic ancestry C282Y homozygotes (mean 64.6 years) and 234 age, sex, and BMI-matched controls without common HFE haemochromatosis variants were included. Lateral vertebral assessment scans (iDXA, GE-Lunar) were acquired at imaging reassessment (2014-2020) and reviewed, blind to genotype, for radiological evidence of vertebral fracture. Matched logistic regression models assessed associations between C282Y homozygosity and vertebral fractures. Results: 78 vertebral fractures (16.9%) were identified within 461 participants. Male C282Y homozygotes had increased odds of vertebral fracture (n=22/89, 24.7%) compared to participants without HFE alleles (n=9/90, 10.0%); Odds Ratio [OR]: 2.95, 95%CI: 1.28-6.85, p=0.01. The association persisted after excluding individuals with a diagnosis of haemochromatosis (OR: 3.37, 95% CI: 1.41-8.10, p=0.007). No excess fracture risk was observed in female C282Y homozygotes (n=23/138, 16.7%) vs those without HFE alleles (n=24/144, 16.7%); OR: 0.99, 95%CI: 0.53-1.87, p=1.00. Conclusion: In this community-based imaging study, male HFE C282Y homozygotes had a markedly higher likelihood of vertebral fractures than those without HFE variants. These findings support further evaluation of vertebral fracture assessment in C282Y homozygous men to ensure prompt treatment to prevent future fracture if appropriate.